The non‐steroidal anti‐inflammatory drug diclofenac sodium induces abnormal embryogenesis and delayed lethal effects in early life stage zebrafish ( Danio rerio )
The non‐steroidal anti‐inflammatory drug diclofenac sodium induces abnormal embryogenesis and delayed lethal effects in early life stage zebrafish ( Danio rerio )
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非甾体类抗炎药双氯芬酸可诱导斑马鱼（Danio rerio）胚胎发育异常和延迟致死效应
DOI：
10.1002/jat.3752
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发表时间：
2018
影响因子：
3.3
通讯作者：
Tatarazako Norihisa
中科院分区：
文献类型：
--
作者：
Horie Yoshifumi;Yamagishi Takahiro;Yagi Ayano;Shintaku Yoko;Iguchi Taisen;Tatarazako Norihisa
双氯芬酸钠是一种广泛用于人用和兽药的非甾体抗炎药，已在水生环境中检测到;因此，需要阐明其对水生生物的生态毒理学效应。最近，从动物福利的角度出发，建议使用斑马鱼（Danio rerio）胚胎进行毒性试验;因此，我们研究了使用胚胎发育期间观察到的亚致死终点预测暴露于双氯芬酸钠的早期生命阶段斑马鱼致死效应的适用性。从受精后2小时至孵化后30天暴露于双氯芬酸钠（0.4 - 7.0 mg/L）后，在7.0 mg/L暴露组中观察到胚胎发生异常，特征为存在水肿和身体弯曲，但在包括对照组在内的任何其他组中均未观察到。身体弯曲被认为是脊柱发育异常的结果。所有异常胚胎均立即孵化，但在孵化后1周内死亡，表明胚胎发生期间水肿和脊柱发育异常的亚致死终点组合可预测暴露于双氯芬酸钠的早期生命阶段斑马鱼的致死效应。需要进一步调查以核实这些调查结果。胚胎发生、存活和生长终点的无明显影响浓度值分别为3.5、1.8和>3.5 mg/L。
Diclofenac sodium, a non‐steroidal anti‐inflammatory drug widely used in both human and veterinary medicine, has been detected in aquatic environments; therefore, its ecotoxicological effects on aquatic organisms need to be clarified. Recently, toxicity testing using zebrafish (Danio rerio) embryos has been recommended from the point of view of animal welfare; therefore, we investigated the suitability of using sub‐lethal endpoints observed during embryogenesis for predicting lethal effects in early life stage zebrafish exposed to diclofenac sodium. After exposure to diclofenac sodium (0.4‐7.0 mg/L) from 2 hours post‐fertilization to 30 days post‐hatching, abnormal embryogenesis, characterized by the presence of edema and body curvature, was observed in the 7.0 mg/L exposure group but not in any other groups including controls. The body curvature was found to be the result of abnormal development of the spine. All abnormal embryos hatched without delay, but died within 1 week after hatching, suggesting that the combination of the sub‐lethal endpoints of edema and abnormal development of the spine during embryogenesis may predict lethal effects in early life stage zebrafish exposed to diclofenac sodium. Further investigations to verify these findings are needed. The value of the no observed effect concentrations for the embryogenesis, survival and growth endpoints were 3.5, 1.8 and >3.5 mg/L, respectively.